Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity.

Abstract

A series of sildenafil analogues and aniline substituted pyrazolo[4,3-e][1,2,4]triazine sulfonamides were prepared and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors and for their anticancer activity against two human breast cancer cell lines (MCF-7, MDA-MB-231). The new compounds were ineffective as CA I inhibitors, poorly inhibited CA II, but were more effective against the tumor-associated isoforms CA IX and XII, with some compounds acting as low nanomolar inhibitors. Evaluation of the cytotoxicity by using an MTT assay, the inhibition of [(3)H]thymidine incorporation into DNA as well as collagen synthesis inhibition, demonstrated that these sulfonamides exhibit cytotoxic effects on breast cancer cell lines ex vivo.

• Authors: Mariusz Mojzych, Anna Bielawska, Krzysztof Bielawski, Mariangela Ceruso, Claudiu T Supuran
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 9 Pg. 2643-7 (May 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24713308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Carbonic Anhydrase Inhibitors
• Pyrazoles
• Sulfonamides
• Triazines
• pyrazole
• Carbonic Anhydrases

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, toxicity)
• Carbonic Anhydrases (chemistry, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• MCF-7 Cells
• Pyrazoles (chemistry)
• Sulfonamides (chemical synthesis, chemistry, toxicity)
• Triazines (chemistry)